Inhibition of succinic dehydrogenase and F0F1-ATP synthase by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS).
This study shows that incubation of rat liver mitochondria in the presence of the thiol/ amino reagent 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) is followed by inhibition of both succinate supported respiration and oxidative phosphorylation. Half-maximal inhibition of succinic dehydrogenase activity and succinate oxidation by mitochondria was attained at 55.3 and 60.8 microM DIDS, respectively. DIDS did inhibit the net ATP synthesis and ATP<=>[32P]Pi exchange reaction catalyzed by submitochondrial particles in a dose-dependent manner (Ki = 31.7 microM and Ki = 32.7 microM), respectively. The hydrolytic activities of uncoupled heart submitochondrial particles and purified F1-ATPase were also inhibited 50% by 31.9 and 20.9 microM DIDS, respectively.
Bernardes
C F
CF
Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Brazil.
Meyer-Fernandes
J R
JR
Martins
O B
OB
Vercesi
A E
AE
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D008929:Mitochondria, Heart / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology*; D010101:Oxygen Consumption; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D013367:Submitochondrial Particles / Q000201:enzymology*; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification
D004791:Enzyme Inhibitors; D013385:Succinate Dehydrogenase; D006180:Proton-Translocating ATPases; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid